Single-nucleotide polymorphisms of HLA and Polygonum multiflorum -induced liver injury in the Han Chinese population

• Published in: World journal of gastroenterology : WJG Vol. 26; no. 12; pp. 1329 - 1339
• Main Authors: Yang, Wan-Na, Pang, Li-Li, Zhou, Ji-Yuan, Qiu, Yuan-Wang, Miao, Liang, Wang, Shou-Yun, Liu, Xiang-Zhong, Tan, Kang-An, Shi, Wan-Wan, Wang, Gui-Qiang, Hou, Feng-Qin
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 28.03.2020
• Subjects: Adult; Aged; Asian Continental Ancestry Group - genetics; Case Control Study; Case-Control Studies; Chemical and Drug Induced Liver Injury - genetics; China; Fallopia multiflora - adverse effects; Female; Genetic Markers - genetics; Genetic Predisposition to Disease - genetics; HLA Antigens - genetics; HLA-A Antigens - genetics; HLA-B Antigens - genetics; HLA-B35 Antigen - genetics; HLA-DRB1 Chains - genetics; Humans; Male; Middle Aged; Odds Ratio; Polymorphism, Single Nucleotide; China; HLA-B35:01; rs202047044; rs111686806; rs1055348; Drug-induced liver injury; Single-nucleotide polymorphism; Polygonum multiflorum
• ISSN: 1007-9327; 2219-2840; 2219-2840
• DOI: 10.3748/wjg.v26.i12.1329

is one of the leading causes of herb-induced liver injury in China. is reported to be a potential biomarker of -induced liver injury (PM-DILI). However, little is known about the relationship between single-nucleotide polymorphisms (SNPs) and PM-DILI. To identify SNPs that indicate susceptibility to PM-DILI. We conducted a systematic study enrolling 382 participants from four independent hospitals, including 73 PM-DILI patients, 118 patients with other drug-induced liver injury (other-DILI) and 191 healthy controls. Whole-exome sequencing was performed for 8 PM-DILI patients and 8 healthy controls who were randomly selected from the above subjects. Nineteen SNPs that showed high frequencies in the 8 PM-DILI patients were selected as candidate SNPs and then screened in 65 PM-DILI patients, 118 other-DILI patients and 183 healthy controls using the MassARRAY system. high-resolution genotyping was performed for the 73 PM-DILI and 118 other-DILI patients. The Han-MHC database was selected as a population control for analysis. < 6.25 × 10 after Bonferroni correction was considered significant. The frequencies of rs111686806 in the gene, rs1055348 in the gene, and rs202047044 in the gene were significantly higher in the PM-DILI group than in the control group [27.2% 11.6%, = 1.72 × 10 , odds ratio (OR) = 3.96, 95% confidence interval (CI): 2.21-7.14; 42.5% 8.6%, = 1.72 × 10 , OR = 13.62, 95%CI: 7.16-25.9; 22.9% 8.1%, = 4.64 × 10 , OR = 4.1, 95%CI: 2.25-7.47]. Only rs1055348 showed a significantly higher frequency in the PM-DILI group than in the other-DILI group (42.5% 13.6%, = 1.84 × 10 , OR = 10.06, 95%CI: 5.06-20.0), which suggested that it is a specific risk factor for PM-DILI. rs1055348 may become a tag for with 100% sensitivity and 97.7% specificity in the PM-DILI group and 100% sensitivity and 98.1% specificity in the other-DILI group. Furthermore, was confirmed to be associated with PM-DILI with a frequency of 41.1% in the PM-DILI group compared with 11.9% ( = 4.30 × 10 , OR = 11.11, 95%CI: 5.57-22.19) in the other-DILI group and 2.7% ( = 6.22 × 10 , OR = 62.62, 95%CI: 35.91-109.20) in the Han-MHC database. rs111686806, rs1055348, and rs202047044 are associated with PM-DILI, of which, rs1055348 is specific to PM-DILI. As a tag for , rs1055348 may become an alternative predictive biomarker of PM-DILI.